Icaritin Soft Capsule Combined With Lenvatinib and TACE for the Treatment of Hepatocellular Carcinoma

Hepatocellular Carcinoma Clinical Trial

Official title:

Icaritin Soft Capsule Combined With Lenvatinib and Transcatheter Arterial Chemoembolization（TACE） for the Treatment of Hepatocellular Carcinomaunresectable, Non-metastatic Hepatocellular Carcinoma

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05903456
• Other study ID #: IRB-2022-802
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: July 2023
• Est. completion date: December 2025

Study information

• Verified date: June 2023
• Source: Zhejiang Cancer Hospital
• Contact: guoliang Shao, doctor
• Phone: 13958183472
• Email: shaogl[@]zjcc.org.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The investigators design a phase II clinical study to explore the efficacy and safety of Transarterial Chemoembolization (TACE) + Lenvatinib + Icaritin soft capsules in patients with Unresectable, non-metastatic hepatocellular carcinoma and to analyze potential biomarkers of therapeutic response.

Description:

This is a single-center, open-label, prospective, non-randomized clinical trial. We adopted the prospective cohort study to explore the safety and efficacy of Transarterial Chemoembolization (TACE) + Lenvatinib + Icaritin soft capsules in the patients with Unresectable, non-metastatic hepatocellular carcinoma.

It is estimated that 20 patients who met the study criteria will be enrolled in Zhejiang Cancer Hospital. The investigators will follow up and collect subjects' data monthly to evaluate the efficacy and safety of treatment, including overall survival and time to progression. Multi-omics data analysis will be used to find potential biomarkers of treatment response.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 20
• Est. completion date: December 2025
• Est. primary completion date: May 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

1. Between the ages of 18 and 80;

2. Patients with histological/cytological confirmed hepatocellular carcinoma.

3. HCC patients eligible for China liver cancer staging (CNLC) Stage IIIa, which cannot be resectable, are not suitable for radical treatment.

4. According to the RECIST v1.1 standard, there must be at least one measurable lesion on the upper abdominal enhanced CT or MRI.

5. Child-Pugh grade A or B;

6. ECOG physical condition score is 0 or 1;

7. Suitable for the indications of TACE surgery and chemotherapy drugs prescribed in advance by the research center, without any contraindications.

8. Regular antiviral therapy should be given if HBV or HCV infection is present.

9. Life expectancy is more than 3 months

10. Able to swallow and absorb oral tablets;

11. Appropriate organ function with the following laboratory test values obtained within 7 days prior to therapeutic use:

12. (hemoglobin value =80g/L, neutrophil count =2.5×109/L, platelet count =75×109/L, serum total bilirubin =2× upper limit of normal (UNL), aspartic transferase =2×UNL, alanine transferase =3×UNL, serum creatinine =1.5×UNL)

13. Manageable blood pressure

14. Women of childbearing age must already be using reliable contraception or have had a negative pregnancy test (serum or urine) within 7 days prior to enrollment and be willing to use an effective method of contraception during the trial period and within 2 months after the last drug administration. Male subjects whose partners are women of childbearing age should use effective methods of contraception during the trial period and within 2 months after the last dose;

15. The subjects voluntarily joined the study, signed the informed consent, had good compliance, and cooperated with follow-up.

Exclusion Criteria:

1. Formation of portal vein main cancer thrombus or extensive cancer thrombus.

2. HCC was treated with local treatment of existing lesions (e.g., TACE, ablation, particle, TARE, hepatic arterial infusion chemotherapy, or radiotherapy).

3. Patients who have previously received targeted or immunoreactive anti-tumor therapy for HCC and chemotherapy need to be desensitized for more than one month.

4. Subjects were unable to perform enhanced CT or MRI scans of the liver.

5. Have a history of liver transplantation or are currently candidates for liver transplantation.

6. Patients at high risk for esophageal or gastric variceal bleeding or unproven severe variceal bleeding within the last 3 months.

7. Have bleeding or thrombotic disease or are receiving thrombolytic therapy

8. Study clinically significant hemoptysis or tumor hemorrhage of any cause within 2 weeks prior to initial administration of the intervention.

9. Study of significant cardiovascular impairment in the 12 months prior to initial administration, such as a history of congestive heart failure above NYHA Grade II (Appendix 12), unstable angina, myocardial infarction or cerebrovascular stroke, or arrhythmias associated with hemodynamic instability.

10. There was clinically significant ascites on physical examination, which could not be controlled by drugs.

11. Known to be allergic to any component of icartin soft capsules and lenvatinib preparation.

12. Pregnant or lactating female patients.

13. Other conditions in which participation in the study is not appropriate according to the investigator's judgment.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma

Intervention

Procedure:
• TACE(transcatheter arterial chemoembolization)
TACE treatment is strictly in accordance with the Chinese guidelines for clinical practice of transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (2018 Edition). The patients with HCC were selected according to the inclusion criteria (referring to the conditions of the subjects). The subjects who met the inclusion criteria could enter the study after they signed the informed consent. 4-6 weeks after the first TACE treatment, the resectability criteria were evaluated. If not, the next cycle of TACE treatment was carried out. The general principle is to reduce the number of interventional treatment and extend the interval of interventional operation as far as possible under the condition of controlling the tumor and the survival of patients with tumor.

Drug:
• lenvatinib
Ronvastinib is an orally administered multi-receptor tyrosine kinase (RTK) inhibitor that selectively inhibits the kinase activity of vascular endothelial growth factor (VEGF) receptors, such as VEGF-1, VEGF-2, and VEGF-3, in addition to inhibiting other pro-angiogenic and oncogenic signaling pathways associated with tumor proliferation ,has been approved as a first-line treatment for liver cancer
• Icaritin soft capsules
Icaritin soft capsule is a flavonoid compound extracted from traditional Chinese medicinal materials. It is a new type of small molecule immunomodulator. It is a 1.2 class of innovative Chinese medicine with global independent intellectual property rights. By inhibiting inflammatory signaling pathway and reducing the release of inflammatory factors, the immune microenvironment can be regulated to play an anti-tumor role. At present, it has been approved for first-line treatment of advanced liver cancer, with good efficacy and safety.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Zhejiang Cancer Hospital

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate	It was defined as the percentage of patients with complete response (CR) and partial response (PR) in all patients, and the treatment response was based on the modified response evaluation criteria in solid tumors (recist1.1)	48 weeks
Secondary	progression-free survival	It was defined as the time from successful hepatectomy to recurrence. Patients who withdraw or lose follow-up will be treated as deletion	96 weeks
Secondary	Overall Survival	It was defined as the time from the beginning of treatment to death from any cause throughout the trial. Patients who dropped out or lost follow-up will be treated as deletion, and the known last survival date will be regarded as the last survival time. Patients who survived at the end of the study will also be treated as deletions, and the last known date of survival will be taken as the final survival time	96 weeks
Secondary	Disease Control Rate	It was defined as the Proportion of all subjects receiving study therapy who rated complete response (CR), partial response (PR), and stable disease (SD) as best overall response according to RECIST 1.1 criteria.	48 weeks
Secondary	Duration of Response	It was defined as the period from the date when tumor response was first recorded (as measured by RECIST 1.1 criteria) to the date when objective tumor progression was first recorded (as measured by RECIST 1.1 criteria) or the date of death from any cause.	up to 48 weeks
Secondary	adverse event	The incidence, severity, and serious adverse events associated with medication use were determined by NCI CTCAE v5.0 standards	96 weekes